SMC1A
structural maintenance of chromosomes 1A, the group of MicroRNA protein coding host genes|Cohesin complex|Structural maintenance of chromosomes proteins
Basic information
Region (hg38): X:53374149-53422728
Previous symbols: [ "SMC1L1" ]
Links
Phenotypes
GenCC
Source:
- Cornelia de Lange syndrome 2 (Definitive), mode of inheritance: XLD
- Cornelia de Lange syndrome (Supportive), mode of inheritance: AD
- atypical Rett syndrome (Supportive), mode of inheritance: AD
- Cornelia de Lange syndrome 2 (Definitive), mode of inheritance: XL
- developmental and epileptic encephalopathy, 85, with or without midline brain defects (Strong), mode of inheritance: XL
- Cornelia de Lange syndrome 2 (Strong), mode of inheritance: XL
- X-linked complex neurodevelopmental disorder (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cornelia de Lange syndrome 2; Developmental and epileptic encephalopathy 85, with or without midline brain defects | XL | Cardiovascular | The condition can involve congenital cardiac anomalies, and awareness may allow early management | Cardiovascular; Craniofacial; Musculoskeletal; Neurologic | 16604071; 20358602; 20635401; 26386245; 26752331; 31334757 |
ClinVar
This is a list of variants' phenotypes submitted to
- Congenital muscular hypertrophy-cerebral syndrome (70 variants)
- not provided (15 variants)
- Developmental and epileptic encephalopathy, 85, with or without midline brain defects (6 variants)
- Inborn genetic diseases (3 variants)
- 6 conditions (1 variants)
- Epileptic encephalopathy (1 variants)
- Congenital muscular hypertrophy-cerebral syndrome;Developmental and epileptic encephalopathy, 85, with or without midline brain defects (1 variants)
- Seizure (1 variants)
- SMC1A-related cohesinopathy (1 variants)
- Cornelia de Lange syndrome 1 (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMC1A gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 184 | 195 | ||||
| missense | 16 | 47 | 183 | 13 | 265 | |
| nonsense | 22 | 28 | ||||
| start loss | 0 | |||||
| frameshift | 42 | 50 | ||||
| inframe indel | 15 | |||||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| splice region | 1 | 2 | 20 | 32 | 4 | 59 |
| non coding | 61 | 100 | 42 | 205 | ||
| Total | 87 | 74 | 257 | 297 | 56 |
Variants in SMC1A
This is a list of pathogenic ClinVar variants found in the SMC1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| X-53374157-G-A | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 12, 2018) | ||
| X-53374188-A-G | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53374248-C-A | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53374250-T-C | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53374381-T-A | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53374411-C-T | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 12, 2018) | ||
| X-53374597-T-A | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 12, 2018) | ||
| X-53374614-C-A | Congenital muscular hypertrophy-cerebral syndrome | Conflicting classifications of pathogenicity (Jan 01, 2023) | ||
| X-53374622-C-T | Congenital muscular hypertrophy-cerebral syndrome | Benign (Jan 12, 2018) | ||
| X-53374652-T-C | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 12, 2018) | ||
| X-53374659-C-T | Congenital muscular hypertrophy-cerebral syndrome | Benign (Jan 12, 2018) | ||
| X-53374660-G-C | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53374723-C-T | De Lange syndrome | Likely benign (Jun 14, 2016) | ||
| X-53374748-C-T | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 12, 2018) | ||
| X-53374751-G-A | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53374852-C-A | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 12, 2018) | ||
| X-53374906-A-G | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53375052-C-A | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53375087-A-G | Congenital muscular hypertrophy-cerebral syndrome | Benign (Jan 12, 2018) | ||
| X-53375105-A-G | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) | ||
| X-53375149-GGT-G | De Lange syndrome | Likely benign (Jun 14, 2016) | ||
| X-53375216-A-G | Congenital muscular hypertrophy-cerebral syndrome | Benign (Jan 12, 2018) | ||
| X-53375458-A-G | De Lange syndrome | Likely benign (Jun 14, 2016) | ||
| X-53375522-A-G | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 12, 2018) | ||
| X-53375660-C-T | Congenital muscular hypertrophy-cerebral syndrome | Uncertain significance (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SMC1A | protein_coding | protein_coding | ENST00000322213 | 25 | 48608 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.77e-8 | 0 | 0 | 0 | 0 | 0.00 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 6.45 | 100 | 510 | 0.196 | 0.0000431 | 8229 |
| Missense in Polyphen | 14 | 210.32 | 0.066566 | 3237 | ||
| Synonymous | 0.190 | 171 | 174 | 0.982 | 0.0000127 | 2196 |
| Loss of Function | 6.43 | 0 | 48.1 | 0.00 | 0.00000372 | 831 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint. {ECO:0000269|PubMed:11877377}.;
- Disease
- DISEASE: Cornelia de Lange syndrome 2 (CDLS2) [MIM:300590]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. {ECO:0000269|PubMed:16604071, ECO:0000269|PubMed:17221863, ECO:0000269|PubMed:17273969, ECO:0000269|PubMed:18996922, ECO:0000269|PubMed:19701948, ECO:0000269|PubMed:20358602, ECO:0000269|PubMed:20635401, ECO:0000269|PubMed:24124034}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cell cycle - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);Cell Cycle;miRNA Regulation of DNA Damage Response;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;Retinoblastoma (RB) in Cancer;Constitutive Androstane Receptor Pathway;Nuclear Receptors Meta-Pathway;Pathways Affected in Adenoid Cystic Carcinoma;ATM Signaling Network in Development and Disease;Liver steatosis AOP;mRNA Processing;Regulation of sister chromatid separation at the metaphase-anaphase transition;DNA Damage Response;Signal Transduction;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Reproduction;SUMOylation;Establishment of Sister Chromatid Cohesion;S Phase;Meiotic synapsis;Meiosis;Signaling by Nuclear Receptors;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Cohesin Loading onto Chromatin;Mitotic Telophase/Cytokinesis;M Phase;Estrogen-dependent gene expression;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;ESR-mediated signaling;ATM pathway
(Consensus)
Recessive Scores
- pRec
- 0.251
Intolerance Scores
- loftool
- 0.0219
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.09
Haploinsufficiency Scores
- pHI
- 0.958
- hipred
- Y
- hipred_score
- 0.840
- ghis
- 0.559
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.988
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Smc1a
- Phenotype
- immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- smc1a
- Affected structure
- neural tube
- Phenotype tag
- abnormal
- Phenotype quality
- increased occurrence
Gene ontology
- Biological process
- mitotic sister chromatid segregation;DNA repair;sister chromatid cohesion;mitotic sister chromatid cohesion;response to radiation;stem cell population maintenance;negative regulation of DNA endoreduplication;cell division;meiotic cell cycle;response to DNA damage checkpoint signaling;regulation of mitotic spindle assembly
- Cellular component
- chromosome, centromeric region;kinetochore;condensed chromosome kinetochore;condensed nuclear chromosome;nucleus;nucleoplasm;chromosome;cytosol;cohesin complex;nuclear matrix;meiotic cohesin complex;mitotic spindle pole
- Molecular function
- chromatin binding;RNA binding;protein binding;ATP binding;mediator complex binding;protein heterodimerization activity